The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

Cardiology ; China ; Consensus ; Heart Failure/therapy* ; Humans ; Self-Management ; United States

OBJECTIVES: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.
Child ; Male ; Female ; Humans ; Anemia, Diamond-Blackfan/genetics* ; Pediatric Obesity/complications* ; Glucocorticoids/therapeutic use* ; Prevalence ; Risk Factors ; Ribosomal Proteins/genetics* ; Mutation

Objective: To explore the differences in subsequent analysis between metagenomic and 16Sr DNA sequencing in compositionally characterizing gut microbiota of healthy elderly. Methods: By using a panel study design, five monthly repeated measurements were performed among 76 healthy older people in Jinan City, Shandong Province. Their fecal samples were collected, and genomic DNA was extracted and analyzed through metagenomic and 16Sr DNA sequencing to compare the composition and diversity of gut microbiota. The correlation between species abundance and α diversity was analyzed by Pearson correlation analysis, and the correlation between species abundance and β diversity was determined by Procrustes analysis. Results: The age of 76 participants was (65.07±2.75), and the body mass index was (25.03±2.40) kg/m². There were 38 males and 38 females. A total of 345 fecal samples were obtained from five monthly repeated measurements . Compared with 16S rDNA sequencing, metagenomic sequencing showed more annotated species at each level. The difference in the number of two sequencing species increased with the decrease of the level. Although there were significant differences in species richness between the two sequencing methods. Their species richness was highly correlated at both phylum (r=0.88, P<0.001) and genus (r=0.77, P<0.001) levels. Bacteroidetes and Firmicutes were the common dominant species. Gut microbiota diversity analysis further showed that there was a significantly positive correlation between α diversity (r=0.70, P<0.001) and β diversities (M²=0.84, P<0.05) in the two groups. Conclusion: The annotation efficiency of metagenomic sequencing is much higher than that of 16S rDNA sequencing. The two sequencing methods are consistent in phylum abundance as well as α diversity.
Male ; Female ; Humans ; Aged ; Gastrointestinal Microbiome/genetics* ; DNA, Ribosomal/genetics* ; Feces ; Sequence Analysis, DNA ; Metagenomics ; RNA, Ribosomal, 16S/genetics*

Glioblastoma is the most common intracranial primary malignant tumor, which leads to the poor quality of life of patients and has a high recurrence rate. Chemotherapy is a vital part in the treatment of this disease. Tetrandrine(Tet) is an active ingredient extracted from the root of the Chinese medicinal plant Stephania tetrandra, which has been proved with a wide range of pharmacological effects including anti-tumor. However, there are few studies regarding the effect of Tet on glioma. In this study, MTT and BrdU assays were employed to detect the effect of Tet on the proliferation of LN229 glioblastoma cells; flow cytometry was used to analyze the cycle distribution and apoptosis; plate cloning assay and soft agar colony formation assay were performed to study the colony formation ability of LN229 cells exposed to Tet; scratch assay and Transwell assay were conducted to detect the ability of migration and invasion; Western blot was adopted to the exploration of the molecular mechanism. The MTT and BrdU assays showed that Tet inhibited the proliferation of LN229 cells in a time-and dose-dependent manner. The plate cloning assay and soft agar colony formation assay showed that Tet weakened the colony formation of LN229 cells in vitro; cytometry assay showed that Tet blocked cells in the G_1 phase and promoted cell apoptosis; scratch and Transwell assays proved that Tet inhibited the migration and invasion of LN229 cells; Western blot results showed that Tet down-regulated the expression levels of CDK2, CDK6, cyclin D1, cyclin E1, snail, slug, vimentin, and N-cadherin, while up-regulated the level of E-cadherin. The results indicate that Tet has a certain inhibitory effect on the proliferation, migration, and invasion of LN229 glioblastoma cells, and such effect may be related to the participation of Tet in the regulation of c-Myc/p27 axis and snail signaling pathway.
Apoptosis ; Benzylisoquinolines ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Glioblastoma/genetics* ; Humans ; Quality of Life

OBJECTIVE: To summarize the experiences and outcomes of 108 robot-assisted laparoscopic upper urinary tract reconstruction surgeries conducted by a single surgeon. METHODS: We consecutively and retrospectively reviewed 108 patients who underwent robot-assisted laparoscopic upper urinary tract reconstruction surgeries by a single surgeon from November 2018 to January 2020. The patient demographics, perioperative variables, postoperative complications and follow-up data were recorded. Fifty-three modified dismembered pyeloplasties (MDP), 11 spiral flap pyeloplasties (SFP), 11 ure-teroureterostomies (UUT), 4 lingual mucosal onlay graft ureteroplasties (LMU), 5 appendiceal onlay flap ureteroplasties (AU), 11 ureteral reimplantations (UR), 6 Boari flap-Psoas hitch surgeries (BPS) and 7 ileal ureter replacements (IUR) were enrolled finally. The success was defined as the improvement in subjective pain levels, and the improvement in the degree of hydronephrosis at ultrasound. RESULTS: All the surgeries were successfully completed without open or laparoscopic conversion. The median operative time was 141 min (range: 74-368 min), median blood loss was 20 mL (range: 10-350 mL) and median hospital stay was 4 d (range: 3-19 d) in MDP group, with the success rate of 94.3%. The median operative time was 159 min (range: 110-222 min), median blood loss was 50 mL (range: 20-150 mL) and median hospital stay was 5 d (range: 3-8 d) in SFP group, with the success rate of 100%. The median operative time was 126 min (range: 76-160 d), median blood loss was 20 mL (range: 10-50 mL) and median hospital stay was 5 d (range: 4-9 d) in UUT group, with the success rate of 100%. The median operative time was 204 min (range: 154-250 min), median blood loss was 30 mL (range: 10-100 mL) and median hospital stay was 6 d (range: 4-7 d) in LMU group, with the success rate of 100%. The median operative time was 164 min (range: 135-211 min), median blood loss was 75 mL (range: 50-200 mL) and median hospital stay was 8.5 d (range: 6-12 d) in AU group, with the success rate of 100%. The median operative time was 149 min (range: 100-218 min), median blood loss was 20 mL (range: 10-50 mL) and median hospital stay was 7 d (range: 5-10 d) in UR group, with the success rate of 90.9%. The median operative time was 166 min (range: 137-205 min), median blood loss was 45 mL (range: 20-100 mL) and median hospital stay was 5 d (range: 4-41 d) in BPS group, with the success rate of 83.3%. The median operative time was 270 min (range: 227-335 min), median blood loss was 100 mL (range: 10-100 mL) and median hospital stay was 7 d (range: 5-26 d) in IUR group, with the success rate of 85.7%. CONCLUSIONS The surgeon performed and modified numerous complicated upper urinary tract reconstruction surgeries by the robotic platform, which facilitated the development of the standardized upper urinary tract reconstruction surgical technique.
Humans ; Laparoscopy ; Retrospective Studies ; Robotic Surgical Procedures ; Surgeons ; Treatment Outcome ; Ureter

Objective:To explore the effect and mechanism of Tuina on denervated skeletal muscle atrophy. Methods:A total of 77 male Sprague-Dawley rats were randomly divided into sham group (n = 7), model group (n = 35) and Tuina group (n = 35). The latter two groups were established skeletal muscle atrophy model by exposing and cutting off the common tibial nerve of rats. One day after modeling, the lower limbs of the surgical side received Tuina in Tuina group. Separately, the surgical side of gastrocnemius muscle were sampled on the 0th, 7th, 14th, 21st and 28th^{day after modeling, and measured the wet mass ratio. The cross-sectional area and diameter of muscle fiber were measured after HE staining. The mRNA expression of autophagy-realated factor Beclin-1, vacuolar protein sorting (Vps34) and microtubule-associated protein light chain 3 (LC3) were tested with reverse transcription real-time quantitative polymerase chain reaction. Results:There was no statistical difference in the ratio of gastrocnemius wet weight, the cross-sectional area and diameter of muscle fiber, and the mRNA expression of Beclin-1, Vps34 and LC3 among three groups on the 0th day (F < 1.321, P > 0.05). Compared with the sham group, the ratio of gastrocnemius wet weight, the cross-sectional area and diameter of muscle fiber decreased at different time points in the model group and Tuina group (P < 0.05), the ratio of gastrocnemius wet weight was higher, and the cross-sectional area and diameter of muscle fiber were bigger, both except on the 21st day, in Tuina group than in the model group (P < 0.05). Compared with the sham group, the mRNA expression of Beclin-1, Vps34 and LC3 increased at different points in the model group than in Tuina group (P < 0.05), and all the mRNA expression was higher, except on the 14th day, in Tuina group than in the model group (P < 0.05). The ratio of gastrocnemius wet weight, the cross-sectional area and diameter of muscle fiber showed a trend of progressive decrease with time in the model group and Tuina group (P < 0.05). The mRNA expression of Beclin-1 and Vps34 increased (P < 0.05), and the mRNA expression of LC3 increased in the model group 21 days after intervention (P < 0.05). The mRNA expression of Beclin-1, Vps34 and LC3 increased first and then decreased, except the mRNA expression on the 14th day in Tuina group (P < 0.05). Conclusion:Tuina may promote the activation of autophagy by up-regulating the expression of autophagy-realated factor Beclin-1, Vps34 and LC3, remove the damaged organelles and proteins, provide certain synthetic substrate and energy for muscle fiber regeneration, thereby reduce the loss of degree of denervated skeletal muscle atrophy.}

OBJECTIVE: To evaluate the feasibility and effectiveness of the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis in the treatment of upper urinary tract urothelial carcinoma (UTUC), and to review the experience of renal autotransplantation for UTUC treatment. METHODS: One case of applying the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis to the UTUC treatment was reported, and related literature was reviewed. The patient was a sixty-four-year old man who received right radical nephroureterectomy for right ureteral carcinoma 1 year before and diagnosed as left ureteral carcinoma(G2, high grade) this time. In order to preserve his renal function and avoid the shortness of common kidney-sparing surgery, a totally extraperitoneal procedure, including retroperitoneoscopic nephrectomy, ureterectomy, renal autotransplantation and Boari flap-pelvis anastomosis, was performed to the patient. RESULTS: The operation was completed successfully without perioperative complications. The renal function recovered to preoperative level within 1 week. No deterioration of renal function during the follow-up and no tumor recurrence was observed under cystoscopy at the 3-month postoperative consult. CONCLUSION The totally extraperitoneal renal autotransplantation with Boari flap-pelvis anastomosis is a feasible and effective treatment for UTUC. The innovative procedure has several advantages compared to the former ones. The extraperitoneal procedure results in significantly less pain, shorter hospital stay, decreased overall time to recovery and lower bowel complications risk without warm ischemia time extension. Meanwhile, the Boari flap-pelvis anastomosis simplifies the follow -up protocols and creates an easy route for cystoscopy and topical therapy. From the systematic clinical analysis, as well as the related literature review, it's been concluded that the renal autotransplantation can be a reasonable option for the patients who have UTUC in solitary kidney or have bilateral UTUC. This type of treatment possesses advantages of preservation of renal function and total resection of malignant lesions. But long-term data and large cohort study on renal function or tumor recurrence are still absent which will be necessary to confirm the advantages of this approach.
Anastomosis, Surgical ; Cohort Studies ; Humans ; Kidney Neoplasms ; Male ; Neoplasm Recurrence, Local ; Nephrectomy ; Pelvis ; Transplantation, Autologous ; Ureter ; Ureteral Neoplasms